Bacterial cell culture processes have been developed for the growth of single cell bacteria, yeast and molds which can be characterized as encased with a tough cell wall. Large scale culture of bacterial type cells is highly developed and such culture techniques are less demanding and are not as difficult to cultivate as mammalian cells. Bacterial cells can be grown in large volumes of liquid medium and can be vigorously agitated without any significant damage.
Mammalian cell culture, however, is much more complex because such cells are more delicate and have a more complex nutrient requirement for development. Mammalian cells cannot withstand excessive turbulent action without damage to the cells and must be provided with a complex nutrient medium to support growth.
In co-pending application, Ser. No. 07-213558, filed Jun. 30, 1988 (MSC-21293-1) and Ser. No. 07-213558, filed Jun. 30, 1988 (MSC-21294-1), systems are shown where mammalian cells are grown in a culture media containing micro-beads and the cells attach to the beads which are suspended in a culture media.
In each such system a culture media is contained in an elongated cylindrical member which is rotated slowly about a horizontal axis while dissolved oxygen was permeated through an elongated annular permeation member for replenishing oxygen in the culture media. While such systems have provided excellent results for cells which attach to microbeads in order to grow, it was found that there was difficulty in culturing cells in suspension without microbeads. It was discovered that the oxygen transmission into the culture media is so slow that effective cell growth does not occur in an annular volume spaced as much as one inch from the permeation member. If agitation is introduced to the system to assist the oxygen transmission, the agitation is counterproductive to cell growth and free aggregation of suspension type cells in that the cells are damaged and disruptive mechanical forces are introduced. Thus, the volume and spatial arrangement of cell growth obtained in such agitated suspension systems has been limited.
In summary, while bio-reactors used to culture mammalian cells utilize mechanical parts, air or fluid movement as a lift mechanism to achieve particle suspension, such mechanisms induce damage and disruptive forces to growing suspension type cells or 3-dimensional cellular structures such as tissues either directly or indirectly by fluid shear.